ReviewFamilial dilated cardiomyopathy: A multidisciplinary entity, from basic screening to novel circulating biomarkers
Section snippets
Imaging diagnosis
The most advantageous cardiovascular imaging tests for patient management are TTE and cardiac MR. TTE provides basic information for DCM such as left ventricle dimensions and function but also provides information about other chambers. Cardiac MR, with a higher spatial resolution, is considered a key imaging test for cardiomyopathies. A complete cardiac exam with MR imaging is entirely non-invasive and enables the assessment of measures with clinical interest in a single diagnostic test. In
Genetics
Since 2009, the American Heart Failure guidelines include recommendations on genetic counseling and genetic testing in patients and families with certain cardiomyopathies. Almost 50% of familial DCM cases have been shown to be associated with a genetic alteration in at least one of the over 60 genes linked to this disorder (Table 2). As shown in Fig. 4, most of these genes codified proteins related to cell structure, ion channels and desmosomes. Most familial cases of DCM are transmitted in an
Novel biomarkers: non-coding RNAs
Patients may benefit from an accurate, accessible and non-invasive test when being screened for familial DCM. Currently, there are no blood-based biomarkers available for monitoring cardiac alterations in patients with familial DCM. The development of a blood-based diagnostic and prognostic test to predict and/or monitor cardiac abnormalities during the subclinical stages of the disease could meet the clinical needs of the cardiologists.
MicroRNAs (miRNAs) are a family of small RNAs (19–25
Conclusions
Here, we highlight the relevance of multidisciplinary teams for the management of familial DCM. Imaging biomarkers can detect the presence of the disease but are of little value for characterizing the earlier stages of the disease when the disease is not yet clinically apparent. Genetic biomarkers provide insights into disease susceptibility. Nonetheless, genetic testing does not supply any information about whether subclinical disease has developed yet or not. Circulating biomarkers could
Perspectives
- –
The combination of different methodologies is fundamental for a proper diagnosis of familial DCM. Management of familial DCM will require collaboration among multidisciplinary teams with representation from multiple different specialties.
- –
The definition of echocardiography patterns specific for each genetic alteration would be of diagnostic and prognostic utility for risk stratification of familial DCM. New imaging techniques could contribute to clinical management. Furthermore, the application
Conflict of interest
The authors declare no conflict of interest.
Disclosures
None.
Author contributions
All of the authors have approved the final version of this article. All of the authors have made substantial contributions to the following: (1) the conception of the article and a critical review of the bibliography, (2) the drafting of the article or revising it critically for important intellectual content, and (3) the final approval of the version to be submitted.
Acknowledgements
This work was supported by the Fundación Pública Andaluza Progreso y Salud para la Financiación de la I + i Biomédica y en Ciencias de las Salud en Andalucia (PI-0011/2014) and the FIS PI14/01729 from the Instituto de Salud Carlos III, which are co-financed by the European Regional Development Fund (ERDF). DdG-C was a recipient of a Sara Borrell grant from the Instituto de Salud Carlos III (CD14/00109). RT was a recipient of a Basic Grant from the Spanish Society of Cardiology (0005-2014). Thanks
References (131)
- et al.
Genetic causes of dilated cardiomyopathy
Prog. Pediatr. Cardiol.
(2014) - et al.
Clinical and genetic issues in dilated cardiomyopathy: a review for genetics professionals
Genet. Med.
(2010) - et al.
Update 2011: clinical and genetic issues in familial dilated cardiomyopathy
J. Am. Coll. Cardiol.
(2011) - et al.
Genetic evaluation of cardiomyopathy—a Heart Failure Society of America practice guideline
J. Card. Fail.
(2009) - et al.
Dilated cardiomyopathy: normalized multiparametric myocardial strain predicts contractile recovery
Ann. Thorac. Surg.
(2015) - et al.
Left ventricular sphericity independently predicts appropriate implantable cardioverter–defibrillator therapy
Heart Rhythm.
(2016) - et al.
Relation between left ventricular shape and exercise capacity in patients with left ventricular dysfunction
J. Am. Coll. Cardiol.
(1993) - et al.
Performance of 3-dimensional echocardiography in measuring left ventricular volumes and ejection fraction: a systematic review and meta-analysis
J. Am. Coll. Cardiol.
(2012) - et al.
Myocardial strain measurement with 2-dimensional speckle-tracking echocardiography: definition of normal range
JACC Cardiovasc. Imaging
(2009) - et al.
Subclinical myocardial dysfunction in patients with reverse-remodeled dilated cardiomyopathy
J. Am. Soc. Echocardiogr.
(2012)
Molecular and cellular correlates of cardiac function in end-stage DCM: a study using speckle tracking echocardiography
JACC Cardiovasc. Imaging
Variation in left ventricular regional wall stress with cine magnetic resonance imaging: normal subjects versus dilated cardiomyopathy
Am. Heart J.
Dobutamine stress testing as a diagnostic tool for evaluation of myocardial contractile reserve in asymptomatic or mildly symptomatic patients with dilated cardiomyopathy
JACC Cardiovasc. Imaging
Left ventricular versus biventricular dysfunction in idiopathic dilated cardiomyopathy
Am. J. Cardiol.
Prognostic usefulness of the tricuspid annular plane systolic excursion in patients with congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy
Am. J. Cardiol.
Reduced right ventricular ejection fraction as a marker for idiopathic dilated cardiomyopathy compared with ischemic left ventricular dysfunction
Am. Heart J.
Non-ischemic dilated cardiopathy: prognostic value of functional mitral regurgitation
Int. J. Cardiol.
Mild vs severe pulmonary hypertension before heart transplantation: different effects on posttransplantation pulmonary hypertension and mortality
J. Heart Lung Transplant
Left ventricular filling in dilated cardiomyopathy: relation to functional class and hemodynamics
J. Am. Coll. Cardiol.
Pseudonormal mitral filling pattern predicts hospital re-admission in patients with congestive heart failure
J. Am. Coll. Cardiol.
A novel titin mutation in adult-onset familial dilated cardiomyopathy
Am. J. Cardiol.
A novel mutation in lamin a/c causing familial dilated cardiomyopathy associated with sudden cardiac death
J. Card. Fail.
Prevalent cardiac phenotype resulting in heart transplantation in a novel LMNA gene duplication
Neuromuscul. Disord.
Cardiovascular magnetic resonance, fibrosis, and prognosis in dilated cardiomyopathy
J. Am. Coll. Cardiol.
Native T1 mapping in differentiation of normal myocardium from diffuse disease in hypertrophic and dilated cardiomyopathy
JACC Cardiovasc. Imaging
Magnetic resonance spectroscopy in myocardial disease
JACC Cardiovasc. Imaging
Hypertrophic cardiomyopathy: a paradigm for myocardial energy depletion
Trends Genet.
MicroRNAs in stress signaling and human disease
Cell
TWIST1 regulates the activity of ubiquitin proteasome system via the miR-199/214 cluster in human end-stage dilated cardiomyopathy
Int. J. Cardiol.
Expression of microRNA-208 is associated with adverse clinical outcomes in human dilated cardiomyopathy
J. Card. Fail.
A cellular microRNA, let-7i, is a novel biomarker for clinical outcome in patients with dilated cardiomyopathy
J. Card. Fail.
microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers
Clin. Investig. Arterioscler.
Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy
J. Am. Coll. Cardiol.
Circulating microRNAs levels in Chinese heart failure patients caused by dilated cardiomyopathy
Indian Heart J.
miRNA-548c: a specific signature in circulating PBMCs from dilated cardiomyopathy patients
J. Mol. Cell. Cardiol.
Circulating microRNA as a biomarker for recovery in pediatric dilated cardiomyopathy
J. Heart Lung Transplant
Classification of the cardiomyopathies: a position statement from the European Society of Cardiology working group on myocardial and pericardial diseases
Eur. Heart J.
The natural history of acute dilated cardiomyopathy
Trans. Am. Clin. Climatol. Assoc.
The failing heart
Nature
The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy
N. Engl. J. Med.
Idiopathic dilated cardiomyopathy: computerized anatomic study of relationship between septal and free left ventricle wall
Rev. Bras. Cir. Cardiovasc.
Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging
J. Am. Soc. Echocardiogr.
The clinical applications of contrast echocardiography
Eur. J. Echocardiogr.
Familial dilated cardiomyopathy: current challenges and future directions
Glob. Cardiol. Sci. Pract.
Diagnostic value of tissue Doppler parameters in the early diagnosis of cardiomyopathies
Herz
Tenting area reflects disease severity and prognosis in patients with non-ischaemic dilated cardiomyopathy and functional mitral regurgitation
Eur. J. Heart Fail.
Left ventricular remodelling and torsional dynamics in dilated cardiomyopathy: reversed apical rotation as a marker of disease severity
Eur. J. Heart Fail.
The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy
Circulation
Diagnostic accuracy of echocardiography for pulmonary hypertension: a systematic review and meta-analysis
Heart
Prognostic value of pulmonary hypertension in ambulatory patients with non-ischemic dilated cardiomyopathy
Circ. J.
Cited by (23)
Emerging role of microRNAs in dilated cardiomyopathy: evidence regarding etiology
2020, Translational ResearchCitation Excerpt :In this context, a multidisciplinary approach is required to reach the diagnosis. Many health professionals should be involved, including cardiologists, radiologists and geneticists.7 Nonetheless, overlapping phenotypes often make differential diagnosis unclear.
HAND2 loss-of-function mutation causes familial dilated cardiomyopathy
2019, European Journal of Medical GeneticsCitation Excerpt :Moreover, DCM also confers a significantly increased risk on thromboembolism, cardiac arrhythmia and death (Chen et al., 2016; den Boer et al., 2016; Halliday et al., 2017; Siontis et al., 2017; Weintraub et al., 2017). Although DCM may arise from such secondary causes as coronary artery disease, arterial hypertension and viral myocarditis (de Gonzalo-Calvo et al., 2017; Weintraub et al., 2017), aggregating evidence demonstrates a substantial genetic contribution to familial DCM (McNally and Mestroni, 2017). Up to now, over 100 genes have been related to DCM, of which the most commonly implicated ones are those encode the sarcomeric, cytoskeletal, desmosomal, nuclear envelope, mitochondrial, and RNA-binding proteins (Al-Yacoub et al., 2016; Asadi et al., 2017; Beqqali et al., 2016; Brodehl et al., 2016; Cao et al., 2017; Cuenca et al., 2016; Dal Ferro et al., 2017; Dalin et al., 2017; Esslinger et al., 2017; Hanley et al., 2016; Janin et al., 2017; Jansweijer et al., 2017; Long et al., 2016, 2017; McNally and Mestroni, 2017; Petropoulou et al., 2017; Qiu et al., 2017; Rafiq et al., 2017; Reinstein et al., 2016; Sabater-Molina et al., 2016; Toro et al., 2016; Truszkowska et al., 2017; Xu et al., 2017; Yuan et al., 2017, 2018; Zhao et al., 2016; Zhao et al., 2016; Zhou et al., 2017).
Genomic characterization in dilated cardiomyopathy
2019, Revista Portuguesa de CardiologiaA new discovered gene mutation in a child with dilated cardiomyopathy
2021, Cardiology in the YoungTeen pregnancy in the setting of familial dilated cardiomyopathy: a case report
2022, BMC Pregnancy and ChildbirthProspective analysis of myocardial strain through the evolution of Chagas disease in the hamster animal model
2022, International Journal of Cardiovascular Imaging